I'm glad to see this question get posted, I was afraid that this particular subtopic of drug chemistry was taboo on this site.  Which would be a shame, because it can be an interesting topic, and maybe relevent to some readers lives.*

Prepuce: Are there definative reasons that make you so confident that this is an issue specific to the pseudoephedrine medication?
Recent discussions on some other forums have made me very doubtfull of the generally assumed fears of secret foilants being added, as described in various patents.  The patents came about because there was some belief that they might become usefull in the future, but for a number of reasons, I'm not the only one that's pretty sure that 'extraction foilants' and 'reaction foilants' are not being added to the pill formulations.

My educated guess, to answer your question, is that first of all it's not true that only a 65% yielding extraction can be done.  If one devoted themselves to the task, I'm sure an extraction in the upper 90%'s could be performed.  But considering the context that today's pseudophedrine pill extractors are in, 65% ends up being a wise compromise.  Because the most common application for wanting to extract pseudoephedrine., commonly requires a certain degree of purity, which for whatever reason often desires a degree of time/labor efficiency, as well as finnancial consideration of solvents, equipment, and so on and so forth.

Because loosely speaking, the body performs an A/B extraction on such medicinal amines, pills are formulated to slow down, and draw out the onset and duration of availability that the drug will have on one's organism.  Be it time-release or not.  So by itself, the very idea of doing an A/B extraction on a medicine that has been formulated into pills is a bit of a challenge.





*Here's a juicy example, a poster named HeadStrong over on the UK drugs forum site, puts his vast expertise to use in his posts regarding pill extraction.  He has made a mini-science of it, that is on a drastically higher level than I've ever seen anywhere else.  The example is that he sounds damn sure about there being a specific complication when polysorbate 80 is present in a HI based reduction of pseudoephedrine.  He says that a different strange, toxic amine is formed, with very little of anything else being yielded.  My friend can attest to experiencing a very specific allergic reaction, when he had ingested certain substances, that according to headstrong's claim, where very likely to have been contaminated by this strange amine.  This very allergic reaction had been experienced by this friend, when ingesting a high tech, recent adulterant commonly found in street bought meth.  Namely Isopropylbenzylamine HCl, a non-psychoactive, structural isomer of meth, that has almost all physical properties identical to that of meth, so say DEA microgram journal forensics chemists.  Nifty stuff, ain't it?

I want to point out to Iknowit that the 65% observation goes back to the time when the gaks were nothing like they are today. In those days guar gum caused big headaches, as did povidone. I believe that the procedure known as the tetra trap originated as an answer to PEG when it was introduced.

There's little doubt that other ingredients are added as foilants and not mentioned on the list of inactives. I don't believe I ever seen a box listing Eudragit, for example, but we know it's used.

The point of all this is like Geez says. The rule of thumb applied then and it still holds today.

As  a final note I'll say that i've seen the solvents remaining after an A/B extraction evapporated down to dryness, yet the missing PSE was nowhere to be found. Maybe it remained in the spent pillmass, but if it did it defied all efforts to retrieve it.

The idea that the remaining 35% remains available for extraction by the correct means may be partially true, but it seems that the bulk of it is converted to something else. I'd like to understand why and how.

PP

Iknowit, the suggestion of performing extractions by mimicking the chemistry of the human body has been discussed for years, and tried several times. I can recall mention of trying pork intestine, natural lambskin condoms, tyvek and others, with varying degrees of success. None of them were apparently good enough to catch on.

The foilants/denaturants I was referring to are things like microcrystalline cellulose, colloidal silicon dioxide, metal salts, povidone, PEG, polysorbate 80 (AKA Tween 80) and other polysorbates, etc., etc. All of these are found in one medication or another, but some of them, singly or in combination, have been added to PSE as reaction foiilants or hindrances to extraction. In fact the heavy restrictions placed on the sale of pse was delayed because the pharmaceutical companies thought that no one would be able to extract pills with these ingredients. Some are listed as inactive ingredients on labels, some are in there but not listed.

I think it's recognized that time release formulations use encapsulation of ingredients to do the job. Some are designed to dissolve in the stomach, some in the upper intestine, others in the lower. Rate of absorption can be controlled. No doubt the additional coatings add to the difficulty of extraction, but that's not to say that they were added for the purpose. Grinding of the pills is one way of breaking through time release coatings, hence the warning on the boxes not to chew the pills. (Who would do that anyway?) I think we're saying about the same thing.

The body may well use a more efficient method of A/B extraction, I don't know. I've been talking about using NaOH, KOH, NaCO3, for basing and using HCl to form the salt, and wondering if there could be a better way, or if there's something particular about PSE that prevents better than a 65% return.

OTOH, the body may only be able to extract 65% of the PSE. If that's the case the dosage has been adjusted to provide the targeted blood level of the drug. Or it could be that no one knows, and the dosage was determined through trial and error. The point is that we can't assume that the body is able to extract 100% of the drug.

Overall you may be right, Iknow, but there's quite a bit of evidence suggesting that there's something else going on.

PP

dfro2, it seems to be the case that an acid/base extraction of psuedoephedrine HCl from pills yields about 65% at a maximum, more often less.

iknowit, since I'm thinking about it, I have seen publications describing efforts to use various inactive ingredients as  impediments to extraction and reaction foilants. Not long before restrictions on sales of psuedoephedrine went into effect there was a paper describing the tetra trap in some detail, and referring to it as one of the "ingenious" ways MA cooks had used to get around extraction deterrent additions to pills.

Addition of inactive substances for this purpose may not be so obvious in time release formulations, but look at some that are not. There was a time when the PSE from 30 mg "red hots" could be cleanly extracted with methanol. They aren't like that today because of a long list of additional materials they now contain. When these efforts first began, they added things like guar gum and povidone. After that came PEG, then mixes of various weight PEGs, then all hell broke loose with polymers, acrylics, metals and metal salts, sugars, etc. Like Eudragit these materials mostly all had some existing use as a pill inactive--otherwise there would have been a lot of safety testing required. Prior to that time, however, most had not been used in PSE containing pills.

Don't take my word for it, though. There used to be several of these papers around, some written both by pharmaceutical companies and others by LE. At least one must have survived the great database crash at WD.

PP

After studying every board on the net for years, trying and believing every pill extraction school of philosophy, I finally arrived at a happy ending reading HeadStrongs theories and procedures.

His understanding is full, but his ideas are simple and efficient.
All the other great thinkers have over complicated the topic and lost sight of reason...

I think a pill thread/section should be allowed only if HeadStrong moderates it.

We are all members at (many)other sites where pill extraction is flogged to death.Do you realy need to bring it here? What is the plus side of doing so?
I agree that extraction could be concidered an art of sorts, but surely there are enough sites already dealing with this in depth.

O

@iknowjt, it was too much for me , but thank you

We are all members at (many)other sites where pill extraction is flogged to death.

Yes it's true.

Do you realy need to bring it here?

First answer;No.

What is the plus side of doing so?

1. Benefit for administrator;
Localized. Make something easier to control something, imagine like; gambling is legalized in certain city, will make the goverment easier to control gambling. I clearly said "but i can see disadvantages if we let it grow, will be so many pills threads and worse...Only one thread, so if a new member post about it then an administrator can easily merge her post/threat or delete if nothing new and announce her about this rule."

2. benefit for "pills extractor"
they can discuss freely in that one threat.

Do you realy need to bring it here?

Second answer; Do you realize this thread is about what???

I agree that extraction could be concidered an art of sorts, but surely there are enough sites already dealing with this in depth.

I said "...this topic is so simple, already discussed till death, but no answer, no proper answer in all forum in the net.

If one attacks each and every known ingredient on the basis that it is soluble in something other parts of the matrix are insoluble in, then one can find answers to even the most difficult problems.

If two substances have similar solubility then there's no available solvent can separate them sharply like what you said. For this case fractional crystallization will be more effective. But any kind of crystallization will be failed if they form salt complex.

(although it may be worthwhile checking the chromatographic separation of similar amines, it is getting to that point)

YES! That's it!
So many routes is discussed in this business but separation is rarely discussed, do you think available work up procedures are proper enough to separate amine from similar amines? I think not.

The diminishing returns + the associated headfuck involved in sourcing sufficient pills to make it worthwhile cleaning the gaacks off glassware, mean that pill extraction is no longer worth the risk involved. For 1 or 2 grams max (and so many people are cooking less, fucking nanos Undecided) you risk 20 years.

What's worth for 20 years?

Put it this way, you would be better served boosting several chemists at a time, because by the time they catch you the armed robberies will be included in the cooking sentence and you'll at least have enough raw material to make it worthwhile

.
I think it's a bit too far...i clearly enough explain what i mean.

The polymers used to bind the aminoalcohol in place will not be removed by a simple pill wash and while 65% gets thrown around I have yet to see so much as a melting point cited by way of characterization.

The polysorbate (read TWEEN) 80 and 20 polymers hold the active moiety in place by having attraction sites for both the hydrophobic and hydrophilic regions. The degree of crosslinking will affect the rate of degradation and with it the release of the drug.

The degradation of these polymers is studied and these studies are released for public consumption. It is not easy for the pharmaceutical industry to change these due to having to conduct clinical trials for bioavailability and to carry out safety testing on the in vivo degradation products of the cleverly designed polymers. Or GAAKS if you will.

These were originally added to frustrate the LWR (alright also there were probably legitimate medical uses for these too and commercial incentives) as they contain a relatively high number of ether bonds which will scavenge the HI generated by the RP and Iodine. The key to these polymers is that they are designed to degrade at certain temperature and pH ranges otherwise they would be useless since no-one wants to deliver 65% of the pill load to a patient.


These polymers are not indestructible and can be cleaved at the ester group  since they are not chemically inert. I think the key here is physical degradation   .

 The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid ... [see ref 1 below ]

I believe these are the primary chemicals of concern while polymers like PEG are also used as binders in the pharmaceutical industry. The days of a methanol wash are gone because people keep asking questions about these damned pills online.

I am not for censorship and if questions were phrased such that the chemistry involved was discussed not just crude protocols with no objective data then this would be a little less frustrating for me. There is a good reason that no correct answer is posted in its entirety on the internet and that is the same reason these polymers changed in the first place  

Headstrong and Prepuce seem like they know about chemistry and probably know more than I do. That said there will be no straightforward chemical way to remove the bound ephedrine from these polymers. Reconstructing a human digestive system is not possible though one could mimic some of the  digestive reactions in vitro. Perhaps a long acid digestion with agitation following transfer to a more basic environment as a start.

I think this could be discussed once it was phrased correctly and that would be along the lines of "removing a phenylaminoalcohol from a large crossmesh of polyethyleneoxides and ether bridges" - Not a mention of AB of pills since those days are now over. That said I neither moderate or administrate on this site and will follow the instructions as they appear. The pill questions can surface as a blight as many of you already know. They may be overlooked if the chemistry were presented and no mention made of name brand OTC cleaners etc. If I had my way such details wouldn't make it as far as the vacuous posts forum lest they mess up the search engine [/rant]

@Iknowjt:

*Here's a juicy example, a poster named HeadStrong over on the UK drugs forum site, puts his vast expertise to use in his posts regarding pill extraction.  He has made a mini-science of it, that is on a drastically higher level than I've ever seen anywhere else.  The example is that he sounds damn sure about there being a specific complication when polysorbate 80 is present in a HI based reduction of pseudoephedrine.  He says that a different strange, toxic amine is formed, with very little of anything else being yielded.  My friend can attest to experiencing a very specific allergic reaction, when he had ingested certain substances, that according to headstrong's claim, where very likely to have been contaminated by this strange amine.  This very allergic reaction had been experienced by this friend, when ingesting a high tech, recent adulterant commonly found in street bought meth.  Namely Isopropylbenzylamine HCl, a non-psychoactive, structural isomer of meth, that has almost all physical properties identical to that of meth, so say DEA microgram journal forensics chemists.  Nifty stuff, ain't it?

The RP/I reduction of PSE leads to a number of other substances and I have a nice paper on this though it is as out of date as the technique. Even if pure PSE were used the product would not be due to a number of side reactions. I imagine that these are increased in the presence of polymer degradation products. In fact I wouldn't doubt it for a second.

[quote Which is based on the idea that time release technology is sopisticated, and it functions on a physical, not just chemical level.  Sort of like coatings, inside of coatings, inside of coatings.  And these coatings actually have a set time to work, so the best way to extract the active ingredient of a pill would be to build a model of the human body, preferebly from reycled components from the cemetery/morgue.  65% Is roughly the amount of the ingredient that a congested customer should feel set in at first, and the remaining 35% is left to stretch it out.  So most likely having a pseudo-stein monster, would still yield only 65%, unless one had the patience to actually wait out the 12 hours or whatever, that the pills are intended to last for.  

This is probably the case and it is not as difficult as one may think to get polymers of varying composition to form in layers - this is established pharmaceutical technology.
 
@ Prepuce1

I don't believe I ever seen a box listing Eudragit, for example, but we know it's used.

There is never a requirement for pharmaceutical companies, within the FDA territories at least, to list the excipients and these are often of a secretive and proprietary nature for many reasons.

@ akom

It's a basic solubility issue just like any sort of recrystallization I'd imagine.  Whenever you extract, some of your PSE is left behind in the layer you discard.

It is more complicated than that and it comes under the branch of science known as posology. Evapping a layer to dryness will tell you whether or not you had something left in it.

@headstrong

YES! That's it!
So many routes is discussed in this business but separation is rarely discussed, do you think available work up procedures are proper enough to separate amine from similar amines? I think not.
 

I think that chromatography can separate even enantiomers so resolution will not be your constraint. Capacity will be an issue and you will still have to break the attraction between the PSE and the polymer.



@ the staff of thevespiary

Could you please make a ruling on whether or not this discussion is welcome before it gets started? Many thanks and I agree with the post before mine This place has some great minds and it is a pleasure to bee here. One way or another lets keep it that way


As Geez said the 65% is practically a bunk figure and at best refers to uncharacterized outdated extraction techniques. It should not be relied upon

----------------------------------------------------------------------------- [reference 1 ]

Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics:
Structure and Degradation Pathways

BRUCE A. KERWIN

Journal of Pharmaceutical Sciences
Vol 97, No 08 p 2924

DOI 10.1002/jps.21190



ABSTRACT: Polysorbates 20 and 80 (Tween1 20 and Tween1 80) are used in the formulation of biotherapeutic products for both preventing surface adsorption and as stabilizers against protein aggregation. The polysorbates are amphipathic, nonionic surfactants composed of fatty acid esters of polyoxyethylene sorbitan being polyoxyethy-lene sorbitan monolaurate for polysorbate 20 and  lyoxyethylene sorbitan monooleate for polysorbate 80. The polysorbates used in the formulation of biopharmaceuticals are mixtures of different fatty acid esters with the monolaurate fraction of polysorbate 20 making up only 40–60% of the mixture and the monooleate fraction of polysorbate 80making up >58%of themixture. The polysorbates undergo autooxidation, cleavage at the ethylene oxide subunits and hydrolysis of the fatty acid ester bond. Autooxidation results in hydroperoxide formation, side-chain cleavage and eventually formation of short chain acids such as formic acid all of which could in?uence the stability of a biopharmaceutical product. Oxidation of the fatty acidmoietywhilewell described in the literature has not been speci?cally investigated for polysorbate. This review focuses on the chemical structure of the polysorbates, factors in?uencing micelle formation and factors and excipients in?uencing stability and degradation of the polyoxyethylene and fatty acid ester linkages.


Keywords: polysorbate; Tween; surfactants; stability; degradation; micelle; proteins; protein formulation; excipients; degradation

If the 65% rule holds for many different pill compositions, maybe it's not the pill formulation that's the problem!

It wouldn't be totally unheard of for Big Pharma to lie about that

Lol... nice call ataraman

Again, I mean no offense to anyone.

You have no offense to me. And i'll try to explain when i said "Do you realize this thread is about what???", i didn't mean to offense you, simply i never think this threat is wrong, no forum rule yet about PSE, so you are not wrong. What i mean when stating that is topic about PSE is already posted, and i believe will be posted again, it's a hot topic, can be avoided. Anyhow sorry if look like offense.    

as they contain a relatively high number of ether bonds which will scavenge the HI generated by the RP and Iodine.

Yes it true for polysorbate.

These polymers are not indestructible and can be cleaved at the ester group  since they are not chemically inert. I think the key here is physical degradation  Lips sealed .

That's true for eudragit, and deesterification is important, half way to destination.

The RP/I reduction of PSE leads to a number of other substances and I have a nice paper on this though it is as out of date as the technique. Even if pure PSE were used the product would not be due to a number of side reactions. I imagine that these are increased in the presence of polymer degradation products. In fact I wouldn't doubt it for a second.

I'm agree, HI route (with common ratio of I2 : RP :  PSE : water) actually is a dirty route, and worse if dehydration is occurred and or reduction rate is much lower than halogenation rate.

"I don't believe I ever seen a box listing Eudragit, for example, but we know it's used."
There is never a requirement for pharmaceutical companies, within the FDA territories at least, to list the excipients and these are often of a secretive and proprietary nature for many reasons.

In my place (most) all containing eudragit although not listing. This become a controversy because many people don't know that

the present of eudragit can be determined easily.

I think that chromatography can separate even enantiomers so resolution will not be your constraint. Capacity will be an issue and you will still have to break the attraction between the PSE and the polymer.

I'll explain my statement "YES! That's it!So many routes is..." i mean we should learn more about separation techniques, especially to cromatography, a typo.
For PSE separation from (the most dangerous kinds of) eudragit, i'm agree that "attraction" related to absorbtion base on polarity, probably not as effective because they have similar polarity (as it, and worse after deesterification), maybe size exclusion is the answer.

@ the staff of thevespiary

Could you please make a ruling on whether or not this discussion is welcome before it gets started?

That is the point, the most important is make a decission/rule, personally i think not important what ever it's, just make as soon as possible and lets make it become  right.